Therapeutic Approaches to Nonalcoholic Fatty Liver Disease: Exercise Intervention and Related Mechanisms

Abstract

Exercise training ameliorates nonalcoholic fatty liver disease (NAFLD) as well as obesity and metabolic syndrome. Although it is difficult to eliminate the effects of body weight reduction and increased energy expenditure-some pleiotropic effects of exercise training-a number of studies involving either aerobic exercise training or resistance training programs showed ameliorations in NAFLD that are independent of the improvements in obesity and insulin resistance. In vivo studies have identified effects of exercise training on the liver, which may help to explain the "direct" or "independent" effect of exercise training on NAFLD. Exercise training increases peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) expression, improves mitochondrial function and leads to reduced hepatic steatosis, inflammation, fibrosis, and tumor genesis. Crosstalk between the liver and adipose tissue, skeletal muscle and the microbiome is also a possible mechanism for the effect of exercise training on NAFLD. Although numerous studies have reported benefits of exercise training on NAFLD, the optimal duration and intensity of exercise for the prevention or treatment of NAFLD have not been established. Maintaining adherence of patients with NAFLD to exercise training regimes is another issue to be resolved. The use of comprehensive analytical approaches to identify biomarkers such as hepatokines that specifically reflect the effect of exercise training on liver functions might help to monitor the effect of exercise on NAFLD, and thereby improve adherence of these patients to exercise training. Exercise training is a robust approach for alleviating the pathogenesis of NAFLD, although further clinical and experimental studies are required.

Keywords: biomarkers; exercise protocol; hepatokines; lifestyle modification; organ crosstalk; training protocol.

Figure 1

Systematic review of training protocols. Effect of changes in body mass index (BMI) (A) and diet consultation (B) on liver steatosis measured by ¹H magnetic resonance (¹HMR) imaging in exercise training programs for treating patients with nonalcoholic fatty liver disease (NAFLD). In (A), the blue, red, yellow, and gray dots represent training protocols with aerobic, resistance, aerobic plus resistance, and stretching exercises, respectively. Effects of the total training time (C), protocol period (D), training duration/session (E), and frequency of training (F) on liver steatosis measured by 1HMR imaging in exercise training programs for subjects with NAFLD. Blue, red and yellow dots represent protocols with aerobic, resistance and combined exercise training, respectively.

Figure 2

Classical effect of training on subjects with NAFLD.

Figure 3

Hepatokines and organ crosstalk in exercise training for subjects with nonalcoholic fatty liver disease (NAFLD).